JAK抑制剂AG490对兔创伤性休克致肺损伤的影响

Effects of JAK inhibitor AG490 on lung injury induced by traumatic shock in rabbits

目的本研究将JAK抑制剂AG490应用于兔创伤性休克致肺损伤动物模型，探索JAK抑制剂对兔创伤性休克致肺损伤中肺组织炎症反应的影响。方法建立兔创伤性休克致肺损伤动物模型；HE染色检测肺组织损伤状况；ELISA检测血清中IL-6、IL-1、TNF-α的表达情况；蛋白免疫印迹实验观察肺组织中CC16、JAK2和STA33蛋白的表达情况；RT—PCR实验观察肺组织中Clara细胞分泌蛋白（Clara cell secretionp rotein，CC16）、JAK2和STAT3基因的表达情况。结果HE染色结果显示，与对照组比较，模型组出现明显炎性细胞浸润，而AG490组的炎症反应则减轻；ELISA结果显示，血清中IL-6、IL-1、TNF—α因子的表达在模型组升高，分别从（99．64±6．33）、（65．42±6．71）、（76．95±8．41）pg／mL，上升至0（675．39±26．42）、（498．77±21．58）、（703．82±32．67）pg／mL，差异有统计学意义（P〈0．05）；而AG490组则比模型组下降，分别为（278．51±11．69）、（202．34±18．36）、（257．65±14．18）pg／mL；蛋白免疫印迹实验可见模型组CC16、JAK2和STA33的蛋白表达与对照组比较均明显升高，且差异有统计学意义，而AG490阻断JAK／STAT信号通路后，CC16、JAK2和STAT3的蛋白表达均明显下降；RT—PCR实验结果表明，模型组CC16、JAK2和STA33的基因表达和AG490阻断组CC16、JAK2和STAT3的基因表达趋势与蛋白表达相一致。结论AG490可以通过抑制JAK／STA33信号通路缓解创伤性休克所致肺损伤的发生，并且可以抑制肺部炎症反应。

Objective To investigate the effects of JAK inhibitors on the inflammatory response of lung tissue and the activation of JAK/STAT signaling transduction pathway in lung injury induced by traumatic shock tissue in rabbits by estabhshing the rabbits model. Methods The rabbit model of lung injury induced by traumatic shock was established. The rabbits were divided into three groups： control group, model group and AG490 group. The pathological findings were observed by hematoxylin -eosin staining. ELISA kit was used to detect the expression of IL - 6 in serum. The expressions of CC16, JAK2 and STAT3 mRNA and protein were detected by RT - PCR and Western blotting, respectively. Results Inflammatory cell infiltration was observed in parts of lung of model group, and decreased in AG490 group. The levels of IL - 6, IL - 1, TNF - α in serum were increased in model group and getting down in AG490 group. The protein levels of CC16, JAK2 and STAT3 in model group were significant higher than those in control group, and their levels represented a downward trend in AG490 group. The expressions of these genes represented the same trend as the protein. Conclusion AG490 can alleviate the inflammation and lung injury induced by traumatic shock by inhibiting the JAK/STAT3 signaling pathway.